Chapter 6

Talaro

Louis Pasteur postulated that rabies was caused by a virus (1884)

Ivanovski and Beijerinck showed a disease in tobacco was caused by a virus (1890s)

1950s virology was a multifaceted discipline

Viruses: noncellular particles with a definite size, shape, and chemical composition

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There is no universal agreement on how and when viruses originated

Viruses are considered the most abundant microbes on earth

Viruses played a role in evolution of Bacteria, Archaea, and Eukarya

Viruses are obligate intracellular parasites

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Size range –

most <0.2 μm; requires electron microscope

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Viruses bear no resemblance to cells

Lack protein-synthesizing machinery

Viruses contain only the parts needed to invade and control a host cell

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Capsids

All viruses have capsids - protein coats that enclose and protect their nucleic acid

The capsid together with the nucleic acid are nucleocapsid

Some viruses have an external covering called envelope; those lacking an envelope are naked

Each capsid is constructed from identical subunits called capsomers made of protein

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Two structural types:

Helical - continuous helix of capsomers forming a cylindrical nucleocapsid

Icosahedral - 20-sided with 12 corners Vary in the number of capsomers

Each capsomer may be made of 1 or several proteins

Some are enveloped

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Figure 6.7 Figure 6.8

Viral envelope

Mostly animal viruses

Acquired when the virus leaves the host cell

Exposed proteins on the outside of the envelope, called spikes, essential for attachment of the virus to the host cell

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Protects the nucleic acid when the virus is outside the host cell

Helps the virus to bind to a cell surface and assists the penetration of the viral DNA or RNA into a suitable host cell

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Complex viruses: atypical viruses

Poxviruses lack a typical capsid and are covered by a dense layer of lipoproteins

Some bacteriophages have a polyhedral nucleocapsid along with a helical tail and attachment fibers

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Figure 6.9

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Viral genome – either DNA or RNA but never both

Carries genes necessary to invade host cell and redirect cell’s activity to make new viruses

Number of genes varies for each type of virus – few to hundreds

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DNA viruses Usually double stranded (ds) but may be single

stranded (ss)

Circular or linear

RNA viruses Usually single stranded, may be double stranded,

may be segmented into separate RNA pieces

ssRNA genomes ready for immediate translation are positive-sense RNA

ssRNA genomes that must be converted into proper form are negative-sense RNA

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Pre-formed enzymes may be present

Polymerases – DNA or RNA

Replicases – copy RNA

Reverse transcriptase – synthesis of DNA from RNA (AIDS virus)

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Main criteria presently used are structure, chemical composition, and genetic makeup

Currently recognized: 3 orders, 63 families, and 263 genera of viruses

Family name ends in -viridae, i.e.Herpesviridae

Genus name ends in -virus, Simplexvirus

Herpes simplex virus I (HSV-I)

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General phases in animal virus multiplication cycle:

1. Adsorption – binding of virus to specific molecule on host cell

2. Penetration – genome enters host cell

3. Uncoating – the viral nucleic acid is released from the capsid

4. Synthesis – viral components are produced

5. Assembly – new viral particles are constructed

6. Release – assembled viruses are released by budding (exocytosis) or cell lysis

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Virus coincidentally collides with a susceptible host cell and adsorbs specifically to receptor sites on the cell membrane

Spectrum of cells a virus can infect – host range

Hepatitis B – human liver cells

Poliovirus – primate intestinal and nerve cells

Rabies – various cells of many mammals

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Figure 6.12

Flexible cell membrane is penetrated by the whole virus or its nucleic acid by:

Endocytosis – entire virus is engulfed and enclosed in a vacuole or vesicle

Fusion – envelope merges directly with membrane resulting in nucleocapsid’sentry into cytoplasm

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Figure 6.13

Varies depending on whether the virus is a DNA or RNA virus

DNA viruses generally are replicated and assembled in the nucleus

RNA viruses generally are replicated and assembled in the cytoplasm Positive-sense RNA contain the message

for translation

Negative-sense RNA must be converted into positive-sense message

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Assembled viruses leave host cell in one of two ways: Budding – exocytosis; nucleocapsid binds to

membrane which pinches off and sheds the viruses gradually; cell is not immediately destroyed

Lysis – nonenveloped and complex viruses released when cell dies and ruptures

Number of viruses released is variable 3,000-4,000 released by poxvirus

>100,000 released by poliovirus

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Figure 6.15

Cytopathic effects - virus-induced damage to cells

1. Changes in size and shape

2. Cytoplasmic inclusion bodies

3. Inclusion bodies

4. Cells fuse to form multinucleated cells

5. Cell lysis

6. Alter DNA

7. Transform cells into cancerous cells

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Figure 6.16

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Persistent infections - cell harbors the virus and is not immediately lysed

Can last weeks or host’s lifetime; several can periodically reactivate – chronic latent state

Measles virus – may remain hidden in brain cells for many years

Herpes simplex virus – cold sores and genital herpes

Herpes zoster virus – chickenpox and shingles

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Some animal viruses enter host cell and permanently alter its genetic material resulting in cancer – transformation of the cell

Transformed cells have increased rate of growth, alterations in chromosomes, and capacity to divide for indefinite time periods resulting in tumors

Mammalian viruses capable of initiating tumors are called oncoviruses Papillomavirus – cervical cancer

Epstein-Barr virus – Burkitt’s lymphoma

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Bacteriophages – bacterial viruses (phages)

Most widely studied are those that infect Escherichia coli – complex structure, DNA

Multiplication goes through similar stages as animal viruses

Only the nucleic acid enters the cytoplasm - uncoating is not necessary

Release is a result of cell lysis induced by viral enzymes and accumulation of viruses - lytic cycle

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1. Adsorption – binding of virus to specific molecule on host cell

2. Penetration – genome enters host cell

3. Replication – viral components produced

4. Assembly – viral components assembled

5. Maturation – completion of viral formation

6. Release – viruses leave cell to infect other cells

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Figure 6.17

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Figure 6.18

Figure 6.19

Not all phages complete the lytic cycle

Some DNA phages, called temperate phages, undergo adsorption and penetration but don’t replicate

The viral genome inserts into bacterial genome and becomes an inactive prophage – the cell is not lysed

Prophage is retained and copied during normal cell division resulting in the transfer of temperate phage genome to all host cell progeny – lysogeny

Induction can occur resulting in activation of lysogenic prophage followed by viral replication and cell lysis

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Figure 6.17

Lysogeny results in the spread of the virus without killing the host cell

Phage genes in the bacterial chromosome can cause the production of toxins or enzymes that cause pathology –lysogenic conversion Corynebacterium diphtheriae

Vibrio cholerae

Clostridium botulinum

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Obligate intracellular parasites that require appropriate cells to replicate

Methods used: Cell (tissue) cultures – cultured cells grow in

sheets that support viral replication and permit observation for cytopathic effect

Bird embryos – incubating egg is an ideal system; virus is injected through the shell

Live animal inoculation – occasionally used when necessary

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Figure 6.20

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Figure 6.21

Viruses are the most common cause of acute infections

Several billion viral infections per year

Some viruses have high mortality rates

Possible connection of viruses to chronic afflictions of unknown cause

Viruses are major participants in the earth’s ecosystem

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Prions - misfolded proteins, contain no nucleic acid

Cause transmissible spongiform encephalopathies –fatal neurodegenerative diseases

Common in animals:

Scrapie in sheep and goats

Bovine spongiform encephalopathies (BSE), a.k.a. mad cow disease

Wasting disease in elk

Humans – Creutzfeldt-Jakob Syndrome (CJS)

Extremely resistant to usual sterilization techniques

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Figure 6.22

Satellite viruses – dependent on other viruses for replication

Adeno-associated virus – replicates only in cells infected with adenovirus

Delta agent – naked strand of RNA expressed only in the presence of hepatitis B virus

Viroids – short pieces of RNA, no protein coat; only been identified in plants

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More difficult than other agents

Consider overall clinical picture

Take appropriate sample

Infect cell culture – look for characteristic cytopathic effects

Screen for parts of the virus

Screen for immune response to virus (antibodies)

Antiviral drugs can cause serious side effects

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